DESCRIPTION: (Adapted from applicant's description) The training and research proposed in this application will take place in an environment ideally suited for the development of a clinician research scientist. Dr. Moss' lab is part of the Center for Research on Reproduction and Women s Health . The Center works in conjunction with the Division of Human Reproduction of the Department of Obstetrics and Gynecology to apply basic research in reproductive biology to human infertility. Dr. Turner is a veterinarian certified by the American College of Therio-genology with five years of clinical experience in veterinary reproduction. She has completed the required coursework for her graduate degree and has been working full time on the project described in this application for 1 1/2 years. In the future, Dr. Turner hopes to obtain a faculty position at a University veterinary hospital where she can build on the foundations of this proposal and apply her basic science training to comparative reproductive biology. Due to her association with the veterinary school, she will add the resources of the veterinary hospital to those already present in the Center. Infertility is a significant problem in humans and animals. It is estimated that approximately 20% of human couples are infertile and that in 50% of those couples, the infertility is at least in part attributable to the male. In animals, male infertility can be economically devastating when it occurs in a genetically valuable individual. Reduced or absent sperm motility is a common feature in cases of male factor infertility; however, the molecular mechanisms underlying the formation and function of the mammalian sperm flagellum are poorly understood. The long-term goal of this project is to examine the regulation of motility in the sperm flagellum, the structure which is responsible for moving the sperm to the site of fertilization. In this regard, while sperm numbers and morphology are not reliable indicators of fertilizing ability, it is generally accepted that immotile sperm are incapable of normal fertilization. The specific goals are to use a mouse mutant model that possesses severely impaired sperm motility and sperm axonemal instability to: (1) identify the gene that is affecting axonemal stability, (2) examine the transcriptional and translational regulation of this gene and the role of its associated protein, and (3) identify homologues of the mouse gene in other species. Axonemal phenotypes identical to those seen in this mouse model have been reported both in the sperm of infertile individuals and in other ciliated cells of individuals affected by Retinitis Pigmentosa and Usher s syndrome. In addition to providing information on the molecular mechanisms underlying a specific axonemal disorder, this study will serve as a first step in identifying genes which are involved in establishing and regulating normal mammalian flagellar motility. The results of the study will provide invaluable information on the physiology of normal sperm motility and will lead to the identification of multiple genes that interact to produce gradients of abnormalities in sperm motility such as those commonly seen in infertile males.